Beta-emitting radiocolloids and microparticles were used for several years with some success against peritoneal ascites and microscopic tumor seeds. However, late effects and morbidity due to intestinal toxicity have made these treatments obsolete and chemotherapy has become the standard adjuvant therapy in e.g. ovarian cancer.
There still exists a considerable medical need for new modalities against intracavitary cancer.
Alpha emitters have previously been proposed as a treatment for intraperitoneal cancer. Two types of chemical classes have been proposed, (1) radioimmunoconjugates and (2) micro- or nano-sized particular suspensions. The advantage with the radioimmunoconjugates is the potential for cell specific targeting and the disadvantage is the substantial leakage of product into the bloodstream causing potential systemic toxicity.
The advantage with micro/nano particles and colloids is the potential for improved local retention reducing distant toxicity. On the down side is the potential for in-homogenous dose deposition and radiation hot spots and also whether the particle itself can cause irritation because of inertness to degradation etc.
If microparticles and/or nanoparticles are to be used the choice is if they should be completely stable or slowly degradable.
By using completely stable particles the advantages include low risk of systemic toxicity. Disadvantages include potentially more heterogenous radiation dose distribution and some risk of local toxicity from “hot spots”. Stable radiotherapeutic particles have been used for radioembolization using the high energetic beta emitter 90Y stably labeled to non-degradable glass spheres (TheraSphere™) or resin based spheres (SIR-Spheres™) for treating primary tumors and metastases to the liver. The liver tissue will in this instance shield against toxic radiation to intestines etc.
A second approach would be to use degradable particles slowly releasing some of the radionuclides: Possible advantages includes a more homogenous radiation dose distribution due to improved diffusion of mother nuclides and or short lived daughter nuclides and less tendency for “hot spots” causing local toxicity. Possible disadvantages include potential for systemic toxicity due to possible transport of released radionuclide into the blood and further redistribution. Degradable particles are mostly used for other cytotoxic compounds like chemotherapeutics and not for radionuclides at the moment.
Thus there is a need for an improved delivery system for alpha particle radiation against intracavitary cancers.